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ToolsQuesada-Vázquez, Sergio, Bone, Caitlin, Saha, Shikha, Triguero, Iris, Colom-Pellicer, Marina, Aragonès, Gerard, Hildebrand, Falk, del Bas, Josep M., Caimari, Antoni, Beraza, Naiara and Escoté, Xavier (2022) Microbiota dysbiosis and gut barrier dysfunction associated with non-alcoholic fatty liver disease are modulated by a specific metabolic cofactors’ combination. International Journal of Molecular Sciences, 23 (22). ISSN 1661-6596
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Abstract
The gut is a selective barrier that not only allows the translocation of nutrients from food, but also microbe-derived metabolites to the systemic circulation that flows through the liver. Microbiota dysbiosis occurs when energy imbalances appear due to an unhealthy diet and a sedentary lifestyle. Dysbiosis has a critical impact on increasing intestinal permeability and epithelial barrier deterioration, contributing to bacterial and antigen translocation to the liver, triggering non-alcoholic fatty liver disease (NAFLD) progression. In this study, the potential therapeutic/beneficial effects of a combination of metabolic cofactors (a multi-ingredient; MI) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) against NAFLD were evaluated. In addition, we investigated the effects of this metabolic cofactors’ combination as a modulator of other players of the gut-liver axis during the disease, including gut barrier dysfunction and microbiota dysbiosis. Diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (NAFLD group) or with a combination of metabolic cofactors (NAFLD-MI group), and small intestines were harvested from all animals for histological, molecular, and omics analysis. The MI treatment ameliorated gut morphological changes, decreased gut barrier permeability, and reduced gene expression of some proinflammatory cytokines. Moreover, epithelial cell proliferation and the number of goblet cells were increased after MI supplementation. In addition, supplementation with the MI combination promoted changes in the intestinal microbiota composition and diversity, as well as modulating short-chain fatty acids (SCFAs) concentrations in feces. Taken together, this specific combination of metabolic cofactors can reverse gut barrier disruption and microbiota dysbiosis contributing to the amelioration of NAFLD progression by modulating key players of the gut-liver axis.
| Item Type: | Article |
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| Additional Information: | Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding Information: The authors gratefully acknowledge the support of the Catalan Government through the funding grant ACCIÓ-Eurecat (PRIV2020-EURHEPAD to X.E.), by the Centre for the Development of Industrial Technology (CDTI) of the Spanish Ministry of Science and Innovation under grant agreement: TECNOMIFOOD project CER-20191010 (to A.C.), by the Biotechnology and Biological Sciences Research Council (BBSRC) Gut Microbes and Health BBS/E/F/00044509 (to N.B and F.H.), the BBSRC Institute Strategic Programme Gut Microbes and Health BB/R012490/1 and its constituent project BBS/E/F/000PR10355, and the BBSRC Core Capability Grant BB/CCG1860/1 as well as the BBSRC Institute Strategic Programme Food Innovation and Health BB/R012512/1 and its constituent project BBS/E/F/000PR10347. F.H. is supported by the European Research Council H2020 StG (erc-stg-948219.EPYC). S.Q.-V. is supported by a fellowship from the Vicente Lopez Program (Eurecat) and M.C.-P. is supported by a fellowship 2021 FI_B2 00150. |
| Uncontrolled Keywords: | gut microbiota,gut-liver axis,intestinal permeability,metabolic disease,scfas,catalysis,molecular biology,spectroscopy,computer science applications,physical and theoretical chemistry,organic chemistry,inorganic chemistry ,/dk/atira/pure/subjectarea/asjc/1500/1503 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 16 Jan 2025 01:10 |
| Last Modified: | 16 Jan 2025 01:10 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/98223 |
| DOI: | 10.3390/ijms232213675 |
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